The broad aims of this work are to define the amplitudes and time scales of molecular motions that are crucial for biological function. These motions of interest include intramolecular side chain and backbone fluctuations as well as cooperative bending or breathing events. Translational motions are also crucial and include motions in pores or other confined spaces. Specifically, we propose to test in detail a new hypothesis that describes the control of proton spin-lattice relaxation in molecular solids including tissues that is important for interpretation of magnetic resonance images. We will use amide hydrogen exchange measurements in structurally well-characterized proteins to characterize the effects of stability on protein structural fluctuations. In particular we will measure the pressure and temperature dependence of amide hydrogen exchange rate constants to extract spatially resolved activation enthalpies, entropies, and volumes as a function of protein stability. These data will help define the character of structural fluctuations in proteins and define more clearly the character of the motions that permit reactions within the folded protein structure. We have demonstrated a simple experimental approach to mapping intermolecular contacts in solution using dioxygen and other paramagnetic co-solutes as the probe species. We will apply this experiment to map how oxygen contacts the surfaces of proteins and how it penetrates through folded protein structures. We will use a similar approach to examine solvation of small molecules and map experimentally the effects of electric charge on the nature of intermolecular contacts and compare the experimental maps with computational approaches to electric potential maps in folded proteins. We will apply NMR spin-lattice relaxation rate measurements in the rotating frame to measure protein intramolecular motions in the microsecond range and propose a similar experiment to define the water molecule lifetime distribution for long-lived water molecules that we may now count using magnetic relaxation dispersion measurements. Finally, we will extend work on molecular and nuclear spin dynamics of molecules in confined environments such as small tubes, pores, and locally ordered environments. This problem is important to understanding the spin relaxation in tissue systems, which is a valuable interpretative aid in clinical radiology.